Operational tolerance to skin allografts has been studied in mice and rats. Previous studies have shown that tolerant rats possess reactive lymphoid cells and serum blocking factors directed at allo-antigens of the tolerated graft. Studies undertaken within the last year have demonstrated that cytotoxic cells in tolerant rats are thymus-derived lymphocytes. Studies in the last year have also resulted in the development of assay systems to measure the primary response to allograft antigens in vitro. The optimal conditions for rat cell cultures have been defined. The development of these systems will provide methods to better define the mechanism and site of serum blocking factors. Studies have also been undertaken to determine the genetic control of transplantation tolerance. Several strains of congenic mice, required for such experiments, have been obtained and are currently being bred. The objective of these studies remains to improve understanding of the cellular and humoral host mechanisms involved in the induction and maintenance of transplantation tolerance. The primary objective in the second year of the proposed grant will be to exploit the recently developed in vitro systems to allow for this analysis. BIBLIOGRAPHIC REFERENCES: Wright, P.W., Bernstein, I.D., Hamilton, B., and Hellstrom, K.E. In vitro reactivity in allograft tolerance: Persistence of cell-mediated cytotoxicity and serum blocking activity in highly tolerant rats. Transplantation 19:437-441 (1975). Bernstein, I.D., and Wright, P.W.: Immunologic reactivity in tolerant rats. Transplantation Proceedings VII: 389-391 (1975).